Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Intravenous regional conduction anesthesia: A technique and literature review-Part I CHARLES A. REESE, CRNA, PhD, CDR, NC, USN Portsmouth, Virginia In the first of a two part series on intravenous regional anesthesia (IVRA), the author reviews the history and development of the Bier block technique. He discusses the various intravenous devices and their placement, and investigates the use of tourniquets, as well as the site and mode of action of IVRA. In the wave of enthusiasm and experimentation which followed Koeller's introduction of cocaine as a local anesthetic agent in 1884, a number of regional nerve block techniques were advanced.1 Corning reported experiments with subcutaneous cocaine while Conway advocated the injection of 4% cocaine directly into fracture sites.2 8 Perhaps the first record of cutaneous analgesia as a result of chemicals injected intravascularly is that of Alms, who in 1886 demonstrated the loss of sensation along the course of an artery into which a cocaine solution had been instilled.4 Interestingly, no mention was made of whether intravenous injection was attempted. The duration of action of cocaine was brief and numerous reports appeared describing "poisoning" or shock following the injudicious use of the drug. In 1892, Schleich, hoping to decrease the incidence of toxic reactions, introduced the massive infiltration of dilute cocaine solutions for literally August/1981 all types of surgical procedures. 5 Similarly, the use of the Esmarch bandage as a type of vascular tourniquet became widely used to prolong the duration of cocaine and to lessen its systemic toxic effects. 0 It was not until 1901 however, that Braun suggested the addition of dilute epinephrine to infiltration solutions in order to slow circulatory uptake of the drug.7 By the late 1890s, Halstead and Crile had reported their techniques of regional anesthesia for the upper extremity. 8s- Their approach apparently was not popular as it required the surgical exposure of the brachial plexus and direct injection of cocaine into the nerve roots. The Bier block By the time August Bier introduced his now famous venous anesthesia in 1908, Einhorn had synthesized and Braun had popularized a new, less toxic chemical local anesthetic agent-procaine. 10 1,12 . It comes as no surprise to learn that Bier's work was a direct outgrowth of his interest in "cocainization" of nerves and use of the tourniquet to decrease blood loss during extremity surgery.'l He was so excited by the success of his new technique that he published his work in no less than five separate journals and was able to report on over 100 cases without a single misadventure. A number of anecdotal reports followed Bier's papers but added little new information other 357 than expanding the list of surgical operations for which intravenous regional anesthesia (IVRA) had been shown to be successful. 14, 1 In 1911, Hirschel and Kulenkampff introduced their percutaneous auxiliary and supraclavicular brachial plexus blocks, respectively.'6 17 The apparent popularity of these techniques and the development of safer general anesthetic agents overshadowed Bier's intravenous block. With only a few exceptions, it did not receive further attention in the professional literature for more than half a century. As the popularity of regional conduction anesthesia increased, the complexity, and hence the duration of surgical procedures, required the development of new local anesthetic agents of longer action and lower systemic toxicity. From this demand came Lofgren's development and introduction of lidocaine hydrochloride in 1946, the first of a series of long-acting amide local anesthetic agents. 8s In 1963, Holmes reintroduced IVRA and included several modifications based on the newer technology of intravenous therapy and pneumatic tourniquets.'" In addition, he suggested the use of lidocaine HC1, an idea which is still very popular today. Following Holmes' paper, a plethora of research articles and additional anecdotal accounts glutted the surgical and anesthesia literature. Most have praised the value of IVRA while others have warned of its potential shortcomings or considered it frankly dangerous. In 1965, an editorial in the Journal of the American Medical Association openly condemned the technique. 20 At least two major symposia have explored the state of the art in IVRA. Interestingly, the findings of the first symposium in 1969, which were to have been published as a text, were clouded by the U.S. Federal Drug Administration's denial to approve lidocaine HCI as an intravenous anesthetic. 21 These important papers were subsequently published in Acta Anesthesiologica Scandinavica-Supplementum XXXVI (1969). Reports of the second conference held in 1978, sponsored by the American Society of Regional Anesthesia, appear in their official publication Regional Anesthesia, (Volume #4 Number 1). An interesting historical aside, it was not until 1970, that Colbern suggested the now popular eponymous name Bier Block for the technique of IVRA. 22 Since its inception, and more particularly, its reintroduction, considerable controversy has surrounded several aspects of the IVRA technique. 358 These include conflicting opinions about anatomic placement of injection sites, exsanguination of the extremity, and use of various tourniquet devices. Each of these will be discussed in this article, as well as the role of premedication. A review of the literature regarding the pharmacokinetics of local anesthetics in IVRA will be included in Part II (to be featured in the October AANA Journal). Premedication for the IVRA technique The choice of preanesthetic medication for patients who will receive IVRA does not differ significantly from that chosen for any patient receiving other forms of regional anesthesia. Al- though personal preferences may vary widely, the goal of any premedication regimen should consider the following. Analgesia for the patient in pain preoperatively: Narcotics are presently the agents of choice, however, the recently introduced agonistantagonist analgesic combinations may find an increasing role in the near future. A number of these drugs are available, each with its distinctive advantages as well as disadvantages. One should not consider the technique of IVRA (placement of an intravenous cannula and tourniquet) as indication alone for preanesthetic analgesics. Protection from harmful reflexes: Vagus nerve-induced bradycardia, the so-called vaso-vagal response, is clearly not desirable. The clinical incidence of this event would seem too infrequent to warrant the routine use of vagolytic doses of the parasympatholytic drugs such as atropine sulfate or glycopyrrolate to patients receiving IVRA. Sedation/tranquilization:Egbert has suggested that an informative preoperative visit by the anesthetist who will provide the anesthesia care may significantly reduce the need for preoperative sedative medications.2 3 Such visits are highly recommended, even when minor surgery is planned. Occasionally, the anesthetist will encounter an extraordinarily apprehensive patient who is not sufficiently calmed by the preoperative visit alone. The patient's desire to be "asleep" may in itself cause him to resist conduction anesthesia techniques, thus certain considerations should be made. Sedative-hypnotics or tranquilizers may be used to decrease the emotional reactions some patients may experience when confronted with anesthesia and surgery. In addition to their psychotropic effects, a number of these agents have been shown to protect the central nervous system from the higher blood levels of local anesthetic agents encountered Journal of the American Association of Nurse Anesthetists with large volume regional conduction anesthesia techniques. Some authors advocate parenteral barbiturates (pentobarbital) for prophylaxis against local anesthetic-induced seizures. 24 , 25 It should be appreciated, however, that approximately 70 mg/kg of this medication must be given in this situation, a dosage certainly not without its own complications.26 During the early 1970s, a number of authors demonstrated that equipotent seizure prophylaxis with diazepam produced fewer undesirable cardiovascular and respiratory side effects than barbiturates. 2 730 In spite of the fact that the exact mechanism of this protection is not clearly understood, diazepam has subsequently enjoyed considerable popularity as a sedative-prophylactic premedication for patients receiving large dose regional anesthetic techniques. Munson demonstrated that lidocaine-induced seizures could be successfully aborted by the intravenous infusion of diazepam 0.1 mg/kg with a minimum of cardiovascular and respiratory effects. In a study of primates, De Jong found that 60 minutes following an intramuscular (thigh) dose of diazepam 0.25 mg/kg, the amount of intravenous lidocaine required to cause seizure activity was increased by two-thirds (12.8 mg/kg to 21.1 mg/kg) .32 Unfortunately, the study did not attempt a correlation between plasma diazepam levels and degree of safety provided. Route of diazepam administration Assuming that there may indeed be some correlation of plasma diazepam levels and the degree of local anesthetic-induced seizure protection, the anesthetist should make every attempt to have the patient receive diazepam at a time and in such a manner as to provide high plasma diazepam levels which will coincide with the peak plasma levels of local anesthetic agents. While it is difficult to extrapolate the exact plasma levels of diazepam necessary to provide antiseizure protection, it is known that numerous factors influence its uptake and distribution characteristics, including the route of administration. Kortilla showed that while intramuscular (deltoid) diazepam produced a faster onset (20-30 min) of subjective symptoms of drowsiness than did oral doses, patients reported no perceivable differences at 60 minutes. 33 Plasma levels rose more quickly with the intramuscular injection than with the oral route, but at 60 minutes, the oral dosage had produced higher plasma levels (190 mcg/cc) than did intramuscular (153 mcg/cc). August/1981 The discomfort associated with intramuscular injection and the high incidence of diazepamrelated thrombophlebitis following intravenous administration, apparently caused by its solvent propylene glycol, have favorably influenced the popularity of the oral route.3 4 When advocating the oral administration of diazepam it should be remembered that the rate of dissolution and gastric activity can markedly influence its absorption. Gamble has shown that intramuscular morphine, meperidine or atropine administered concurrently with oral diazepam will prolong the peak absorption time of diazepam from a control of 60 minutes to 90 minutes. It will also decrease the peak blood level attained from a control of 200 mcg/cc to 105 mcg/cc, 135 mcg/cc and 144 mcg/cc, respectively. 85 Gamble's work also suggests that drugs which enhance gastric emptying such as metoclopramide will decrease diazepam's peak absorption rate to less than 30 minutes and increase the peak blood levels attained to 244 mcg/cc. The efficacious, routine use of antacids as preanesthetic medication is well reviewed in the literature, and is commonly used in many anesthetists' practices. Recent work has shown that, in addition to lowering the gastric pH to levels less harmful should aspiration occur, absorption dynamics of concurrently administered oral medications may be favorably altered. Sturdee has demonstrated both a markedly increased uptake and increased plasma diazepam level (120 mcg/cc versus 70 mcg/cc at 30 minutes) when diazepam 5 mg was given orally along with an oral antacid (magnesium trisilicate) .8 It should be noted that at 30 minutes, this surpasses levels obtained by the administration of 10 mg by either the intramuscular or oral routes without antacids. 3" Sturdee postulates that this is due more to decreased gastric emptying time than to a direct effect of the change in stomach pH. In contrast, Nair states that one would expect any antacid which raises stomach pH to near that of the pKa of diazepam (3.3) to enhance absorption of the drug from the stomach.3 7 He found that the concomitant administration of magnesium trisilicate slowed uptake and decreased the clinical soporific effect of diazepam. The use of sodium citrate or aluminum hydroxide hastened this effect. Patients in the aluminum hydroxide group had significantly higher degrees of absorption resulting in higher plasma levels by 60 minutes. To further confuse the issue, Gamble found that the addition of aluminum hydroxide will indeed hasten the absorption of diazepam but that 359 at 60 minutes, diazepam administered alone and orally will produce higher plasma levels. 85 Depending upon your interpretation of this data, it would seem that if the prophylactic effects of diazepam are desired, the drug should be administered approximately 60 minutes prior to the expected administration IVRA. Of course, keeping in mind the incidence of discomfort and vascular thrombotic activity involved, the intravenous administration of diazepam immediately prior to initiating IVRA might be considered. Finally, some would advocate no prophylactic coverage, favoring instead to use this important agent only when CNS symptoms are observed. Moore feels that ventilation with oxygen alone is sufficient should systemic symptoms be noted. 38 He believes that hypoxia and hypercarbia play a significant role in the manifestation of seizure activity and since such activity is short lived, the post-ictal state is worsened by administration of sedative drugs. Regardless of the clinical data presented, preblock therapy with these medications cannot be considered a guarantee against drug induced seizures, nor should their administration be considered a substitute for proper technique. Intravenous devices and their placement As mentioned earlier, Bier's original technique remained essentially dormant for more than 50 years following its introduction in 1908. In defense of this, it must be remembered that his technique must have been considered cumbersome as it re- quired two separate tourniquets and an operative procedure (venous cutdown) for placement of the intravenous cannula (Figure 1) .10 It was not until 1931 that percutaneous venipuncture was advocated, thus making the technique more practical.89 The site of cannula placement is another matter altogether. Bier suggested the injection be made into vessels located in the antecubital fossa, possibly because it was more accessible for surgical exposure, and that the cannula be directed distally in order to force the liquid toward the hand (presumably the surgical site). Such direction of injection is interesting as the presence of valves in the extremity's superficial venous system would seem to create an obstruction to distal flow. Indeed research by Fleming more than half a century later, using radiopaque solutions to study the site of action of intravenous local anesthetics, demonstrated that venous valvular competency could cause retrograde flow, even to the point of leakage beneath a pneumatic tourniquet. From this, there appears to be no advantage in directing an intravenous device distally when performing IVRA. Present concepts of anatomical preference for percutaneous intravenous devices are closely related to the proposed site of action of IVRA. Those who subscribe to the theory that IVRA works by simple diffusion of liquid agents from the intravenous space into the soft tissues, thereby anesthetizing the nerve endings at the tissue level, advocate the placement of the injection site as close to the site of injury or proposed surgery as prac40 44 tical, usually a vein on the dorsum of the hand. Figure 1 August Bier's original technique of Intravenous Regional Anesthesia. Placement of a metal cannula required a surgical procedure which no doubt deterred from its ready acceptance. Of interest is the use of both a distal and proximal tourniquet to isolate the surgical site and to lessen the total volume of injectate. (From Flagg, P.J. The Art of Anesthesia, J. B. Lippincott Co., Philadelphia, Pa. 1932, With Permission.) Proximal Sbandage Distal bandae Esmarch SKIN MARKING OF NOW ISCHEMIC VEIN -- 360 Journal of the American Association of Nurse Anesthetists Advocates of the opposing view, which is that IVRA works at the major nerve trunks in a manner similar to traditional peripheral nerve block techniques, have promulgated the practice of placing the injection site in close proximity to these structures, such as in superficial veins in the antecubital fossa. 46 47 Caution should be taken, however, when injecting at the antecubital fossa as competent valves in the veins may prevent retrograde flow. This would cause injection pressure to surpass that created by the tourniquet, thus allowing liquid anesthetic agent to flow into the general circulation (Figure 2). Sorbie mentions this argument in favor of placing the intravenous cannula in the hand or forearm in spite of his belief that the drug works primarily at the nerve trunk. 47 A slow injection will lessen the risk of this problem as well as preventing possible rupture of the vein. Van Niekerk has reported a similar complication when Figure 2 Distribution of injection in median cubital vein at elbow. Note that contrast remains in vessels near the elbow while no contrast can be seen in the distal third of the forearm. Onset of analgesia is in the typical distal to proximal "glove" pattern, the posterior elbow being last. Note also the presence of contrast above the tourniquet, presumably due to excessive pressure during injection. Such drug enters systemic circulation and may result in symptoms of toxicity. (From Raj, P.P. et al 1972 "The Site of Action of Intravenous Regional Anesthesia," Anesthesia and Analgesia 51:776-781. With Permission.) a long cannula device was placed at the antecubital fossa and threaded to a point proximal to the tourniquet, with resultant systemic injection. 48 Raj has shown that within five minutes of injection, regardless of the site, the majority of liquid injectate concentrates in the large superficial veins of the antecubital fossa (Figure 3) .4 Regardless of the site preferred, the selection of the percutaneous indwelling intravenous device should be made with due care. The technical development of numerous highly flexible cannula devices would seem to antiquate the further use of inflexible metallic needles. Such cannulae are available in virtually all sizes (25-12 gauge) and a myriad of adaptations. It is recommended that a small bore (22-25 gauge) be used as this will reduce the size of rent remaining in the vein when the device is removed and will lessen extravasation of local anesthetic agent into the subcutaneous tissue or out through the skin. By attaching a sterile intravenous extension tubing and syringe of local anesthetic agent, a sterile closed system can be achieved which allows considerable flexibility during exsanguination of the extremity (Figure 4) without fear of dislodgement or infiltration into the subcutaneous tissue. Brown suggests leaving such a system intact during a case in order to conduct a continuous technique. 49 One may wish to employ an indwelling cannula which accommodates a tight fitting obturator stylet or a Heparin-Lok® device (Figure 5) as these will remain in the vein during exsanguination and are less cumbersome to use than the syringe-tubing arrangement. Exsanguination In the years following Holmes' popularization of IVRA, a number of papers appeared which anecdotally described modifications of Bier's original work. Among these were reports exploring the efficacy of exsanguination prior to inflation of the tourniquet. In modern practice this issue is only academic as most surgeons desire a "bloodless field" in which to work, thus requiring careful exsanguination prior to tourniquet inflation. Additionally, the present concept of the site of action of IVRA, which is detailed later, mandates conscientious and complete vascular exsanguination. In current practice a latex Esmarch bandage, an elastic wrap such as an Ace® bandage or a Crepe bandage"0 is wrapped snugly around the extremity from the fingers toward the shoulder. Occasionally this practice is impractical due to pain or an open wound. In such cases a pneumatic August/1981 Figure 3 (A) Distribution of 5cc injected into median cubital veins. Note preferential filling of superficial veins around elbow. (B) Distribution of 15cc injected into dorsum of hand with second tourniquet added to obstruct cephalad spread. Note drug has reached the median and cephalic cubital veins via communicating perforating veins but does not reach the phalanges or extravasate into hand tissue. (From Raj, P.P. et al 1972 'The Site of Action of Intravenous Regional Anesthesia," Anesthesia and Analgesia, 51:776-781. With Permission.) A B orthopedic splint or 3-5 minutes of gravity drain4 . age may be used. 47, 51, 52, Care must he taken when utilizing the Esmarch or elastic bandage as excessive shearing forces (up to 1000 mmHg) may be produced particularly on previously traumatized areas, or exquisitely sensitive skin as found in elderly or cachectic patients. 53 ~"4 Pulmonary embolism has been reported following this type of exsanguination when used for delayed internal fixation of long bone fractures. 55 A number of authors have presented convincing arguments favoring exsanguination with IVRA. 46.1 6.57 Adams has determined the venous volume of the upper extremity below a midhumerus tourniquet to be approximately 170 cc. If this volume were not exsanguinated, the injection of a small volume (40 cc) of a local anesthetic agent into this vascular pool would considerably dilute the agent, making it weak and ineffective.5 8 Atkinson believes this dilution may prevent or severely retard the spread of agent from the vascular bed into surrounding tissue thus re- Figure 4 Closed injection system for Intravenous Regional Anesthesia. A drug-filled 50cc syringe is attached to a sterile intravenous extension tube. Drug is injected into the extension tube and connected to an indwelling intravenous cannulae (22 Ga) and secured. The extremity and injection system is ready for exsanguination of blood. Journal of the American Association of Nurse Anesthetists sulting in a large reservoir of agent available to enter the systemic circulation when the tourniquet is released. 57 Furthermore, Adams also feels that the exsanguinated vascular tree plays a significant role in transport of local anesthetic agents to the nerve substance. Thus, he strongly favors complete exsanguination prior to injection" 8 Bradford has reported that exsanguination of a single upper extremity can increase central venous pressure up to 6 cm H 2 O and advises that caution be used when exsanguination is considered in a patient with a history of congestive cardiac failure. 9 When injecting local anesthetics into the exsanguinated extremity, one will often notice a blotchy appearance of the skin (cutis marmorata) caused by residual blood being forced from deep vessels into small subcutaneous capillaries. 19 This apparently has no clinical significance and is mentioned only so that the anesthetist is aware of its possible occurrence. The anesthetist is reminded that even with complete exsanguination and tight fitting tour- niquets, some vascular leakage may occur via the intramedullary vessels of the humerus and may appear as "oozing" at the operative site. 60 Again, other than being an annoyance for the surgeon, this is apparently of little clinical significance. The use of tourniquets It is perhaps obvious that without the use of a tourniquet, there would not be a technique such as IVRA. However, the physiologic and pharmacologic effects of this device are perhaps the least discussed aspects of the technique. The development of resistive/restrictive tourniquets invariably is linked with the surgical amputation of extremities. As early as the 16th century, Pare advocated such a technique to decrease blood loss and thereby ease the surgical exposure.6 1 In 1718, Petit introduced a screw-type device and coined the term tourniquet from the French tourner, to turn. 62 In the 1860s, Lister became the first to use a tourniquet for a surgical procedure other than amputation.68 Shortly thereafter, Esmarch introduced his eponymous rubber bandage for the dual Figure 5 (A) Alternative system of injection for Intravenous Regional Anesthesia. Once placed, a sterile obturator is inserted into the intravenous cannulae and secured. Following exsanguination the obturator is removed and a drug-filled syringe is connected to the cannula for injection. (B) Placement of a "Heparin Lock" device onto the indwelling cannula allows additional mobility during exsanguination of the extremity. Following this, a syringe/needle isplaced inthe device and injection made. August/1981 purpose of exsanguination and producing ischemia of the extremities. This was later modified by von Langenbeck to its present wide band-like form."6 In 1904, Harvey Cushing revolutionized surgical tourniquets by his development of a pneumatic device to which a manometer and tank of compressed air could be attached, thus creating a controllable constant pressure in the tourniquet. 65 Cushing's idea apparently went unnoticed, at least relative to IVRA, as Bier's original works utilized only the Esmarch bandage. Indeed, even Holmes' work in 1963 mentioned only the application of a single Riva-Rocca type blood pressure cuff as a tourniquet for performing IVRA. 19 In 1964, apparently unaware of Herreros' earlier work, Hoyle introduced a specially designed two66 compartment pneumatic tourniquet for IVRA. * His suggestion was that the proximal compartment be inflated first and IVRA be carried out as usual. After 15-20 minutes, the distal compartment was to be inflated over what was now anesthetized tissues, and the proximal compartment deflated. This concept and device found many ardent advocates and is widely practiced today. Despite the widespread clinical use of pneumatic tourniquets, there is a paucity of experimental and clinical data establishing the duration of ischemia which may be considered safe and the optimum pressure at which a tourniquet should be maintained. In common practice, two hours is often stated as the maximum time a tourniquet can be safely left inflated. This empirical limit apparently dates from Bruner's work in 1951, and has survived essentially unchallenged to date. 68 Prolonged ischemia of an extremity is obviously contrary to physiologic well-being. Following two hours of tourniquet induced ischemia, the venous pH falls in a linear fashion from a normal of 7.4 to 6.9. Venous pO2 falls from a normal of 45 mmHg to a low of 4 mmHg while venous pCO 2 rises from a normal of 35 mmHg to 104 mmHg. 69 Miller has shown that after 60 minutes of tourniquet induced ischemia, tissue pO2 levels are significantly lower than venous oxygen tensions taken at the same interval. 70 Additionally, following release of the tourniquet, tissue gas tensions and pH return to normal levels much more slowly than do venous values. While the clinical application of such data is inconclusive, Adams has shown that irreversible muscle fatigue develops at two hours of ischemia. 1 Webb has demonstrated evidence of cell damage in striated muscle which results in marked increases in capillary permeability to fluid and pro- 67 364 tein. 72 That this fluid loss may be clinically significant is supported by Fine's report of acute renal failure and circulatory shock following release of an extremity tourniquet. 78 Although modern practice of aggressive perioperative systemic fluid therapy generally precludes such disasters, the large shift of protein and fluids following tourniquet ischemia cannot be discounted. The importance of this phenomenon at the microscopic level has only recently been suggested as a course of post-tourniquet sequelae. Miller's work suggests increased interstitial pressure resulting from such edema may be hazardous, particularly when it occurs in muscles which are highly compartmentalized by fascial sheaths, preventing adequate perfusion of these tissues.70 His finding that a six-fold increase in interstitial pressure may persist as long as 24 hours following only one hour of tourniquet ischemia should be noted. Fowler demonstrated nerve conduction delays which he attributed to intramyelin and periaxonal edema which resulted in swelling of the myelin sheath. 74 The somatic and nervous complications resulting from such insults such as the post ischemic hand syndrome have long been recognized by surgeons and should be considered by anesthetists any time a tourniquet has been employed. 7 In contrast to the concept of ischemia related sequelae, another popular opinion is that direct compression of tissues beneath a tourniquet may play a significant role in such complications. In 1954, Moldaver inferred that the decrease in the number of reports of tourniquet-related nerve damage was due to the increased use of the pneumatic tourniquet, the popular rubber tube style of that period. 76 He noted that even with the pneumatic tourniquet, some residual damage did occasionally occur. He described a tourniquet paralysis syndrome which was manifest as functional disturbances in the neural distribution distal to the site of compression which could not be explained on the basis of ischemia alone. Ochoa supports this concept with his demonstration of localized edema in the myelin layer of the compressed segment. 77 Lundborg also demonstrated marked changes in the epithelium of infrafunicular capillaries located beneath the cuff site, more so than nerves in the ischemic limb distal to the compression.78 From the data reviewed, it is difficult to identify a singular causative situation. Quite probably, neural sequelae are a result of a combination of compression and ischemia; changes from com- Journal of the American Association of Nurse Anesthetists pression begin immediately with inflation of the device while ischemic changes develop later. It would be evident that the majority of tourniquet related complications can be avoided by careful attention to technical details. Certainly, misapplied pneumatic tourniquets can produce undue pressure on a concentrated site. When a tourniquet is initially applied too loosely, the fabric cuff may restrict lateral expansion of the rubber bladder, thus narrowing the pressure band as much as 75%. 71 There is no simple direct relationship between the pressure applied at the skin surface and that realized in the interior of the limb. 54 Lundberg has shown that the sciatic nerve may realize a pressure of only 110 mmHg when 700 mmHg is applied over the thigh. Stewart suggests that a tourniquet be applied at the point of maximum circumference, thereby compressing nerves and vessels within the bulk of periosteous muscle rather than direct compression of these vital structures over honey prominences.s8 In this regard, it is generally advised that a tourniquet not be utilized distal to the elbow or knee.el Prior to application of the tourniquet, it is recommended that orthopedic wool (Webrill®) be wrapped circumferentially around the extrem- ity so as to completely cover the area beneath and approximately one inch to either side of the device (Figure 6). 81 The imprint wrinkle which is usually present following deflation and removal of the tourniquet apparently is of little clinical significance. Ecchymosis or blistering of the skin is the most common complication observed following the use of an unpadded tourniquet. 71 Additionally, care should be taken to prevent prepping solutions from pooling under the tourniquet or its padding, 82 84 as serious chemical burns may result. The recommended inflation pressure of a pneumatic tourniquet remains an illusive subject. Such pressures will depend in part on the site of application, size of the limb involved and the patient's systemic blood pressure. Cuff pressures in the range of 250-300 mmHg for the upper extremity and 450-500 mmHg for the lower extremity are widely published and practiced. The derivation of these figures is, however, unclear. Nobel has demonstrated that in the arm, a cuff pressure of 250 mmHg will totally occlude intraneural as well as superficial vasculature in the compressed segment.85 Sanders suggests that arbitrary inflation pressures should not be used. He favors instead a min- Figure 6 Prior to application of the tourniquet a layer of cotton wool (Webrill*) should be placed circumferencially beneath the tourniquet to extend approximately one inch beyond the tourniquet's margins. Care should be taken during the preparation of the extremity not to saturate the padding with antiseptic solutions. August/1981 imum effective pressure (MEP), achieved by adjusting the tourniquet pressure, regardless of the indicated gauge pressure, until distal pulses are no longer felt in the extremity. 86 It must be remembered, however, that systemic arterial pressures may change, often as much as 70-100 torr, particularly if any discomfort is felt. Therefore, some advocate that the MEP be identified and an additional 100 mmHg be added to the tourniquet gauge pressure. 87 This technique has been found clinically satisfactory by the author with no known complications after several hundred procedures. A properly functioning tourniquet is a necessity. This should consist of a double compartment cuff and switching device which is inflation-tested prior to each application (Figure 7) . Additionally, the rubber bladders should be removed from the fabric binder and inspected periodically for deterioration. If there is any question as to their condition, new bladders should be obtained. Before purchasing an inflation device, one must be sure that it will totally satisfy its intended purpose. While numerous styles are available, the author prefers a compressed air or oxygen powered model which includes a constant read pressure gauge and minute timer to remind the user of elapsed time. Portable models are available which will allow patients to be transferred (for example, to the radiology department) with the IVRA intact. Pressure gauges should be tested against a liquid mercury manometer prior to each application and the inflated tourniquet squeezed while observing for a deflection or "bounce" on the pressure gauge. This latter maneuver is done to observe patency of the delivery line and to insure that a "flap valve" effect is not present in the lumen of the delivery tube. Mullick has reported a case in which a pressure gauge displayed 350 mmHg while the tourniquet was pressurized to over 1200 mmHg.88 Prior to initiating IVRA, the anesthetist is advised to consult the surgeon as to projected operative time. If this time plus preparation exceeds two hours, an alternative form of anesthesia is suggested such as brachial plexus block. When employing IVRA, the judicious utilization of time is imperative. The anesthetist should request the surgeon to make any necessary skin marks with an indelible marker prior to the block technique and that he time his scrub and gowning to coincide with the termination of the patient's skin prep. Accordingly, the anesthetist should make sure that a technician is available to commence the skin prep immediately following the injection of local anesthesia. Conservation of this precious time will make a significant contribution toward successful IVRA. The technique of tourniquet deflation plays a significant role in the uptake and distribution Figure 7 (A) Double-cuff tourniquet recommended B for Intravenous Regional Anesthesia. Note that two compartments are combined within one strap, each compartment having a separate inflation nipple. Luer-Lock® fittings are highly recommended to prevent disconnects. Single valving system from which either tourniquet compartment can be individually regulated. With this device a single pressure source (02. compressed air, nitrogen, etc.) can be utilized. 3000 un lus" iMamuNI (B) Pressure regulator and gauge. Gauges on such devices must be checked against a mercury manometer prior to each use. Inaccurate gauges may result in patient injury. A /i;~ * ~ : Journal of the American Association of Nurse Anesthetists of local anesthetic agents following IVRA and will be discussed in Part II of this article. Tourniquet pain Of all complications associated with the use of pneumatic tourniquets for IVRA, the most common and least clearly understood is the occurrence of tourniquet pain. The application of tourniquet compression of approximately 250 mmHg over the upper aspect of an extremity will invariably result in some degree of discomfort after 30-45 minutes. This pain has been attributed to the direct compression of tissues, including nerves and muscle. 89, 90 Subjectively, this pain may vary among patients but is most often intolerable after one hour. While systemic analgesics and hypnotics may attenuate the intensity temporarily, some degree of basal narcosis is often required to make completion of surgery possible. This pain may even be noted during inhalation or intravenous general anesthesia as a narrowing of pulse pressure and a gradual rise in mean blood pressure and pulse rate. August/1981 In order to better understand this phenomenon, the somatic distribution of the upper arm is illustrated in Figure 8. The lower lateral and posterior cutaneous nerves arise from within the brachial plexus and innervate the anterior, lateral and posterior aspects of the upper arm whereas the intercostobrachialis, which innervates the medial aspect, is formed by branches of the second thoracic nerve (T2). Sorbie postulates that the terminal branches of these nerves possess a minimum of vasculature at this point, therefore, their axons are exposed to a minimum of local anesthetic agent when utilizing conventional techniques of IVRA. 47 Expanding this concept, Haas has suggested a second wrap modification wherein the extremity is exsanguinated as usual, the proximal cuff of a double tourniquet is inflated and the Esmarch bandage or elastic wrap is removed."' A local anesthetic agent of choice is injected intravenously and the extremity is then rewrapped in the same manner as the initial exsanguination. The premise of this maneuver is that it will force the liquid injectate into the smaller vasculature, thus exposing the terminal branches of the proximal nerves to the agent, particularly those innervating the skin beneath the distal tourniquet. As these nerves become subcutaneous proximal to the site of an upper arm tourniquet, an effective and technically simple method is a subcutaneous wheal of local anesthetic agent placed around the circumference of the arm just proximal 19 , to the tourniquet. 92 Exploring further the physiology or origin of tourniquet pain, Kuntz had demonstrated that some afferent (somatic) spinal nerve fibers traverse the white communicating rami and are associated with the sympathetic trunk as it enters the dorsal roots of the spinal cord. 93 These afferent fibers are not normally considered in the same functional category as the somatic fibers of the integument and are not found distributed in the skin or muscle. Threadgill has shown that direct noxious stimulation of blood vessels distal to the site of mechanical or chemical somatic disruption will result in afferent conduction of pain. 9 ' From this he hypothesized that small somatic afferent fibers travel in concert with the sympathetic nerves from the vasculature of the extremities. Further, it is known that sympathetic vasomotor nerves play a significant role in pain associated with ischemic extremities. Such pain stimulates an increase in vasomotor tone which in turn results in still further painful ischemia. Chemical or surgical sym- 367 pathectomy has been recognized as therapeutic in resolving this unfortunate situation. From this information the combination of ischemia and chronic compression of vascular innervation is thought to contribute to the afferent transmission of the discomfort known as tourniquet pain. Site and mode of action of local agents The site of action of intravenously injected local anesthetic agents is perhaps the most thoroughly studied but least clearly understood aspect of IVRA. A number of explanations have been advanced in recent years, however, the subject is very abstract and highly vulnerable to statistical manipulation of data for the sake of emphasizing a particular point of view. The proposed sites of action generally emphasize one anatomical location or a combination of locations: (1) peripheral sensory nerve endings; (2) neuromuscular junctions; and (3) major nerve trunks. In addition, a dual mechanism is considered. Peripheral nerve endings: tissue level Bier, using procaine stained with methylene blue, demonstrated that injectate dispersed rapidly throughout the extremity, including the substance of major nerves. 95 He felt that this dispersion was facilitated by the rich vasculature and absence of valves in small vessels (less than 2 mm in diameter) which emerge along the course of the major nerves. From this he concluded that local anesthetics injected intravenously worked at the "end apparatus of the nerves." Using radioisotope labeled lidocaine, Knapp demonstrated that the drug rapidly enters the extracellular fluid and reaches a state of equilibrium within the muscle mass.9" Atkinson suggests that the rapid injection-toonset and tourniquet deflation-to-resolution times and the anatomical pattern of analgesia distribution favor the vascular perfusion of peripheral tissue and sensory nerve endings as the site of action. 7, 97 He suggests that one would not expect to effectively block nerve trunks with the dilute solutions of lidocaine (0.5%) which are clinically employed. He further postulates that the superimposition of acidosis resulting from ischemia may potentiate this effect, thus mimicking a true nerve block. Mazzee suggests that this acidosis increases capillary and venule permeability to the small lidocaine molecule, allowing it to easily escape into the surrounding extracellular fluid and tissue." 368 Atkinson supports this concept with a case report in which IVRA was incomplete in a finger on which the skin and muscle had been avulsed. He felt this indicated that the interruption in vascular flow precluded exposure of these tissues 57 to the local anesthetic agent. ' 97 Using electrophysiologic nerve conduction studies, Miles showed that while a 66% increase in latency of action potential in sensory nerves can be attributed to ischemia alone, there was a 180% increase with the addition of lidocaine."8 Interestingly, the rate of conduction in motor nerves was not affected by ischemia or the combination of ischemia and lidocaine. From this he concluded that intravenously injected local anesthetic agents acted at the sensory nerve ending and not major nerve trunks. Though unclear to what degree, ischemia certainly plays some contributing role in the establishment and maintenance of IVRA. Referring to perfusion studies using radiopaque anesthetic solutions, Fleming implied a strong correlation between the onset and pattern of sensory loss and distribution of opacity in the soft tissues of the arm. 40 She thus proposed the site of action to be at the tissue level. In similar studies, Sorbie and Raj came to quite the opposite conclusion., 5 47 Allen found a localization of agent 6-8 times greater in traumatized tissue than in normal tissue. He felt this was due to easier diffusion of agent via broken capillaries. 99 The neuromuscular junction The neurophysiological studies by Miles yielded interesting muscle response data similar to that found when patients received a nondepolarizing muscle relaxant. It was demonstrated that with lidocaine, a point could be reached at which nerve stimulation failed to generate a muscle response while direct muscle stimulation could still elicit muscle contraction. Unlike the non-depolarizing block, administration of neostigmine to patients blocked with lidocaine did not alter the muscle responses. Considering this and similar results reported earlier by Harvey and Jaco, Miles concluded that lidocaine inhibited production of acetylcholine and opposed its action 98 01 at the neuromuscular junction. , 100oo, To demonstrate the anatomical distribution of intravenously injected drugs, Atkinson used a dilute solution (0.1 mg/cc) of d-Tubocurarine and found profound relaxation of the muscles below the tourniquet. 7 7 Using elaborate electrophysiologic experi- Journal of the American Association of Nurse Anesthetists ments, Fujita demonstrated post-tetanic facilitation during IVRA, especially with procaine and suggests that local anesthetic agents vary in their anticholinesterase activity. He feels that agents are carried via the vessels to the myoneural junction where there is "direct competition between acetylcholine and the local anesthetic agent to occupy the receptor site on the postjunctional membrane." While these demonstrations do not adequately explain the profound analgesia obtained with dilute local anesthetic solutions, the clinical observation of undesirable volitional motor movement during hand surgery has prompted the author to adopt the addition of dilute solutions of a non-depolarizing muscle relaxant (d-Tubocurarine 0.1 mg/cc). This mixture has proven adequate to block all motor activity below the tourniquet and is of little clinical significance when released into systemic circulation following completion of the technique. Nerve Trunks A number of authors have suggested the site of action to be the major nerve trunks as they traverse the tissue distal to the tourniquet. In his original description of IVRA, Bier noted the delayed onset of analgesia in tissue distal to the injection site and isolated by a second tourniquet. 10 He concluded this delay in onset represented block of nerve trunks. Atkinson noted a paresthesia when utilizing IVRA and attributed this to forceful perfusion of intraneural vessels. 57 Using nerve conduction studies to identify the role of ischemia and radiographic studies to determine the vascular distribution of injectates, Sorbie felt that the effects of lidocaine were due to direct contact of the drug with the large nerve trunks. 47 He too implicated the intraneural vasculature as a possible site of this important interface. Using radioisotope-tagged lidocaine to study tissue distribution of IVRA, Cotev found that shortly following injection the concentration in nerve tissue was four times that 0s 104 of muscle or skin. In nerve conduction studies performed by Shanks, motor and sensory conduction velocity delays were attributed to effects of local anesthetics at the nerve trunks. 10' This is in opposition to the conclusion drawn by Miles who felt similar findings were primarily the result of tourniquet ischemia." Combined site of action Bier was the first to suggest a dual mechanism of action for IVRA, stating, "The direct anesthesia in the area between the two tourniquets occurs immediately if one uses Novocain® in sufficient A ugust/1981 amounts. The indirect anesthesia distal to the peri- pheral tourniquet needs some time to develop." 10 His implication was that the direct anesthesia is due to block of peripheral nerve endings in the tissues saturated by local anesthesia agents while the indirect anesthesia distal to the distal tourniquet results from block of the large nerve trunks as they traverse the proximal tissue. Using a combination of clinical investigation techniques, Raj derived convincing documentation for the bi-phasic theory. 45 Following the injection of only 5 cc of radiopaque stained lidocaine (0.5%) solution into a dorsal hand vein, contrast material can be noted in the large superficial veins of the forearm: radial, ulnar and median antebrachial (Figure 3) . Of particular note, even with this small volume, is the presence of contrast in the basilic, cephalic and median cubital veins at the elbow. Additionally, no contrast material is noted distal to the injection site, presumably blocked by venous valves. Only following injection of 30 cc could contrast be noted distally and then only as far as the second set of venous valves at the first proximal phalanx (Figure 9). Figure 9 Distribution of 30cc injected into dorsum of hand. Note that drug has spread distally only as far as the first proximal phalanx. Loss of sensation begins in the digits and travels proximally. (From Raj, P.P., at al 1972 "The Site of Action of Intravenous Regional Anesthesia," Anesthesia and Analgesia 51:776-786. With Permission.) The onset of sensory loss was immediate, beginning first in the digits and traveling proximally toward the anterior and medial aspects of the forearm in a "glovelike" fashion, finally reaching the posterior aspect of the elbow. A total of 10-15 minutes elapsed before any contrast was noted to have extravasated into muscle tissue (Figure 10). When this experiment was repeated with a rubber band-tourniquet occluding the midforearm, the 5 cc volume again passed proximally, presumably via the perforating and interosseous veins, to the level of the elbow (Figure 11). With 15 cc, the majority of contrast was again found at the elbow with only a small amount having extravasated into the hand and wrist. In a similar experiment, injection was made into the medial cubital vein at the elbow. A similar filling pattern and onset of anesthesia was noted as before (Figure 2), with good filling of vessels around the elbow. Virtually no contrast was seen in the distal one-third of the forearm. The presence of contrast intravascularly above the mid-humerus was of particular interest. It is postulated that injection pressure exceeded the tourniquet pressure, allowing proximal flow of Figure 10 local anesthetic into systemic circulation. Transient CNS symptoms were noted in this patient. Similar leakage of solution during forceful injection was 40 radiographically documented by Fleming. In experiments using radioisotope-tagged local anesthetic agents, Adams estimated the intravascular volume of the upper extremity to be 170 cc."' Instillation of 40 cc of local anesthetic will not produce any significant hydrostatic pressure, thus, it will seek the path of least resistance, the large superficial veins. Along with radiographic documentation indicating that contrast does not significantly leave the vascular system for approximately 15 minutes following injection, this must be taken as strong evidence against the concept of localization at the peripheral nerve endings, at least in the early stages of the technique. This does not preclude such a site of action later in the technique. It is interesting to note that regardless of the injection site used, the pattern of onset was the same. This gives rise to further questions concerning the peripheral nerve ending as the site of action. By investigating the microvascularity of peripheral nerves, the proposed site of action can be clarified. DeJong has shown that the fibers which Figure 11 Distribution of 5cc injected into dorsum of hand with occlusive tourniquets on forearm. Note that Distribution of spread 15 minutes following injection of 40cc into dorsum of hand. Note diffusion of drug into the muscle tissue of forearm. Anesthesia of arm was complete within 5 minutes of injection. drug has passed proximally to the elbow via interosseous and perforating veins. (From Raj, P.P., et al 1972 "The Site of Action of Intravenous Regional Anesthesia," Anesthesia and Analgesia 51:776-786. With Permission.) (From Raj, P.P., et al 1972 "The Site of Action of Intravenous Regional Anesthesia," Anesthesia and Analgesia 51:776-786. With Permission.) Journal of the American Association of Nurse Anesthetists serve the distal extremity are located primarily in the middle or core of major nerve trunks while those which serve the proximal tissues are around the mantle or periphery of the trunk (Figure 12) . 10 7 Figures 13 and 14 demonstrate the microvascularity of such a peripheral nerve trunk. The majority of the larger intraneural vessels are located near the "core". Raj postulates that immediately following injection of local anesthetic agent into the exsanguinated and isolated vessels of the extremity, these vascular channels carry the agent to the nerve trunks in the vicinity of the elbow. From there, the fluid flows into the intraneural vessels near the core of the trunk and diffuses into the nerve fibrils due to a concentration gradient. Ten to 15 minutes later, diffusion of the local anesthetic agent into the extracellular fluid of muscle tissue ensues and continues until an equilibrium with the intravascular drug is approached. Sensory perception returns in a similar pattern, proximal to distal, and is similarly explained. When circulation is restored, the drug is first washed from the nerve core, thus restoring the distal sensory distribution. This is followed by removal from the mantle, restoring the proximal segments. Eventually, circulation in the muscle mass will reduce the concentration of the peripheral nerve endings. As these events are telescoped into a 5-15 minute time frame, this obscures the discrimination of events and it is impossible Figure 12 Axons located in the nerve's "mantle" innervate proximal regions, those in the "core" distal regions. Onset of anesthesia is related to the distribution of nerve exposed to local anesthesia agents. Nerve trunk August/1981 to clinically ascertain the differentiation of these two mechanisms. This direct intraneural exposure of the drug also explains why relatively small volumes of very dilute agents can produce profound sensory loss. If applied directly to the outside of a major nerve trunk, the equivalent drug would produce little effect whatsoever. Regardless of the site of action, the onset of analgesia is immediate and generally complete within 5-10 minutes, thus coinciding with completion of the presurgical skin preparation and draping. Part II will focus on local anesthetic agents and principles of pharmcokinetics. It will also investigate complications and contraindications of IVRA as well as special considerations for its use. REFERENCES (1) Koeller C. 1884. The Use of Local Anesthesia on the Eye, Preliminary Report. Rostock Universitiits-Buchdruckeri von Adler's Erben, Translation in Foundations of Anesthesiology by Faulconer and Keys, pp. 773-775, Volume 2. (2) Corning JL. 1885. On the Prolongation of the Anaesthetic Effects of the Hydrochlorate of Cocaine when Subcutaneously Injected. New York Medical Journal 42:317. Conway JR. 1885. Cocaine as an Anaesthetic in Fractures (3) and Dislocations. New York Medical Journal 42:632. (4) Alms H. 1886. Die Wirkung des Cocains auf die peripherischen Nerven. Arch. Physiol. Suppl. Bd. p. 293. (5) Schleich KL. 1892. A New Method of Local Anaesthesia (Infiltration Anaesthesia) . International Clinics (5th series), 2:177-192. (6) Esmarch JFA. 1878. The Surgeons Handbook on the Treatment of Wounded in War, English translation by H.H. Cluton. London: Sampson Low, Marston, Searle & Rivington, p. 127. (7) Braun H. 1901. The Addition of Epinepherine to Cocaine for Local Anesthesia. Archiv fur klinische Chirugie 96:541-591, (Translated in Foundations of Anesthesiology by Faulconer and Keys, Volume 2, pp. 834-842). (8) Halstead WS. 1885. Practical Comments on the Use and Abuse of Cocaine; Suggested by Its Invariably Successful Employment in More Than A Thousand Minor Surgical Operations, New York Medical Journal 42:294-295. (9) Crile GW. 1897. Anesthesia of Nerve Roots with Cocaine. Cleveland Med. ]., 2:355. (10.) Bier A. 1908. Concerning a New Method of Local Anesthesia of the Extremities. Arch Klin Chir 86:1007-1016, (Translated by C.S. Hellijas in Survey of Anesthesiology-Classical File, 11:294-300). (11) Einhorn A. 1899. On the Chemistry of Local Anesthetics. Munchen medicinische Wochenscrift 46:1218-1220, (Translated in Faulconer and Keys, pp. 801-807). Braun H. 1905. Several New Local Anesthetic Agents. (12) Deutsche medizinishe Wochenschrift, 2:1667-1671, (Translated in Faulconer and Keys, pp. 842-847) . Bier A. 1899. Versuche iiber Cocainisrung des Riicken(13) markes. Dtsch. 7. Chir, 51:361. Hirtel F. 1909. Die Technik der Veneanlisthesie. Wien (14) med WVschr, 35:1999. Hitzrot JM. 1909. Intravenous I.ocal Anaesthesia. Ann (15) Surg 50:782. Hirschel G. 1911. Die Anisthesierung des Plexus Brachialis (16) bei Operationen an der oberen Extremitit, Munchen Med Wschr 58:1555. 371 (17) Kulenkampff D. 1911. brachialis, Zbl Chir 38:1337. Die Anasthesierung des Plesus (18) Loifgren N. 1948. Studies on Local Anaesthetics. Xylocaine, a new Synthetic Drug. Stockholm: Ivar Haeggstroms. (19) Holmes C. 1963. Intravenous Regional Analgesia-A Useful Method of Producing Analgesia of the Limbs, Lancet 1:245247 (Feb 2). (20.) Editorial, 1965. Regional Intravenous Anesthesia. JAMA 193:120 (Jul-Sept) . (21) Steinhaus j. 1973. Regional Intravenous Anesthesia. Audio Digest-Anesthesiology Vol. 15 #5. (22) Colbern EC. 1970. The Bier Block for Intravenous Regional Anesthesia: Technic and Literature Review. Anesthesia and Analgesia 49:935-940. (23) Eghert LD, Battit GE, Turndorff H. et al. 1963. The Value of the Pre-Operative Visit by an Anesthetist. JAMA 185: 553-555. (24) Tatum AL, Atkinson AJ, Collins KH. 1925. Acute Cocaine Poisoning: Its Prophylaxis and Treatment in Laboratory Animals. J. Pharmacol. 7'her. 26:325-335. (25) Mazzee RI, Dunbar RW. 1969. Intravenous Regional Anesthesia-A Report of 47 Cases With a Toxicity Study. Acta. Anes. Scandinarv., Supp. XXXVI, p. 27-34. (26) Tatum AL, Collins KH. and Its Treatment (27) Feinstein, in MB, 1926. Acute Cocaine the Monkey. Arci Lenard W, Poisoning Intern Med 38:405-409. Mathias J. 1970. The an- tagonism of local anesthetic induced convulsions by the benzodiazepine derivative diazepain. Arch Int Pharinacodyn 187:144154. (28) Aldrete JA, Daniel W. 1971. Evaluation of Premedicants as Protective Agents Again Convulsive (LD5O) Doses of Local Anesthetic Agents in Rats Anesth. Analg. 50:127-130. (29) DeJong RH, Heavner JE. 1971. Diazepam Prevents Local Anesthetic Seizures. Anest hesiology 34:523-531. (30) DeJong RH, Heavner JE. 1972. Local Anesthetic Seizure Prevention: Diazepam versus Pentobarbital. Anesthesiology 36:449-457. (31) Local Munson ES, Wagman I. 1972. Diazepam Treatment of Anesthetic-Induced Seizures. Anest/hesiology 37:523-528. (32) DeJong RH, Heavner JE. 1974. Diazepam Prevents and Aborts Lidocaine Convulsions in Monkeys. Anesthesiology 41: 226-230. (33) Kortilla K, Linnoila M. 1975. Absorption and Sedative Effects of Diazepam after Oral Administration and Intramuscular Administration into the Vastus Lateralis muscle and the I)eltoid Muscle. Br. J. Anaesth, 47:857-861. (34) Langdon DE, Harlan JR, Bailey RL. 1973. Thrombophlebitis with diazepam used Intravenously. JAMA 223:184-185. (35) Gamble JAS, Gaston JH, Nair SG, and Dundee JW. 1976. Soine Pharmacological Factors Influencing the Absorption of Diazepam Following Oral Administration. Br. J. Anaesth, 48:10911095. (36) Sturdee DW. 1976. Diazepam: Routes of Administration and Rate of Absorption (A Study of Women with Pre-Eclampsia) , Br. J. Anaesth, 48:1091-1095. (37) Nair SC, Gamble JAS, Dundee JW, Howard PJ. 1976. The Influence of Three Antacids on the Absorption and Clinical Action of Oral Diazepam" Br. J. Anaesth, 48:1175-1179. (38) Moore DC, Bridenbaugh LD. 1960. Oxygen: the antidote for systemic toxic reactions from local anesthetic drugs. JAMA, 174:182-847. (39) Morrison JT. 1931. Intravenous Local Anesthesia, British Journalof Surgery, 18:642-647. (40) Fleming SA. Viega-Pires JA, McCutheon RM, et al. 1966. A Demonstration of the site of action of intravenous hignocaine. Can. Anaesthe. Soc. 1. 13:21-27. (41) Ong RT, Kortis HI. 1965. Experiences with Intravenous Regional Anesthesia For Upper Extremity Surgery. Jornaifl of the Newark Bet/i israel Hospital, 16:87-92. (42) Manthey FA. 1965. Intravenous Regional Anesthesia of the Upper Extremnity. Anesthesiology, 26:827-828. (43) Cox JMR. 1964. Intravenous Regional Anesthesia. Cant. Anaes. Soc. . 11:03-508. 372 (44) Dunbar RW, Mazzee RI. 1967. Intravenous Regional Anesthesia-Experience With 779 Cases. Anesthesia and Analgesia, 46:806-813. (45) Raj PP, Garcia CE, Burleson JW, Jenkins MT. 1972. The Site of Action of Intravenous Regional Anesthesia. Anesthesia and Analgesia 51 (5): 776-786. (46) Adams JP, Albert S. 1964. Intravenous Regional Anesthesia in Hand Surgery. Journal of Bone and Joint Surgery 46-A 4, (June) p. 8 1 1 - 8 1 6 . (47) Sorbie C, Chacha P. 1965. Regional Anaesthesia by Intravenous Route. Br. J. Med. 5440:957-960. (48) Van Niekerk JP, De V. Tonkin, PA. 1966. Intravenous Regional Analgesia, S. Afr. Med. j. 40:165-169. (49) Brown EM. 1966, Prolonged Intravenous Regional Anesthesia. Anesthesia and Analgesia, 45:319-321. (50) Pygros NM. Argyopoulos EL., Pygos VN. 1977. The Use of Intravenous Regional Anesthesia for the Reduction of Colles Fractures. Resuscitation (Casualty Surgeons Association Papers) 5:59-63. (51) Finlay H. 1977. A Modification of Bier's Intravenous Analgesia-Use of the Pneumatic Splint. Anaesthesia 32:357-358. (52) Dawkins OS. 1964. Intravenous Regional Anaesthesia. Can. Anaes. Soc. J. 11:243-246. (53) Middleton RWD, Varian JP. 1973. Tourniquet Paralysis, Journal of Bone and joint Surgery. 55B:432. (54) Griffiths JC., Heywood OB. 1973. Biochemical Aspects of the Tourniquet. Hand 5:113-118. (55) Austin M. 1963. The Esmarch Bandage and Pulmonary Embolism. Journal of Bone and Joint Surgery 45-B:384-385. (56) Bell HM. Slater EM. Harris HH. 1963. Regional Anesthesia with Intravenous I.idocaine. JAMA 186:544-549. (57) Atkinson DI, Modell J, Moya F. 1965. Intravenous Regional Anesthesia, Anesthesia and Analgesia 44:313-317. (58) Adams JP, Albert S. 1962. The Blood Volume in the Lower Extremities: A Technique for its letermination utilizing Cr 5 ' tagged red cells. Journal of Bone and Joint Surgery 44A: 489-493. (59) Bradford EMW. 1969. Haemodynamic changes associated with the application of lower leg tourniquets. Anaesthesia 24: 190-197. (60) Furlow I.T. 1971. Cause and Prevention of Tourniquet Ooze. Surg Gynecol Obstet 132:1069-1072. (61) Klenerman L. 1962. The Tourniluet in Surgery. Journal of Bone and Joint Surgery 44B: 937-943. (62) Thompson CJS. 1942. Th/,e History andl Evolution of Surgical Instruments, Schumans Pub. Co. pg. 85. (63) I.ister J. 1909. Collected Papers Volume I, Oxford: Clarendon Press, pg. 176. (64) Von Esmarch, JFA. 1873. Ucher kiinstliche Blutleere bei Operationetn. Sanim lug Klinischcr VortrYge in Verhindung mit Detschen Klinikern. Chirurgie 19(58):373. (65) Cashing H. 1904. Pneumatic Tourniquets: with Especial Reference to their use in Craniotomies, Medical Neus 84:577580. (66) Herreros LG. 1946. Regional Anesthesia by the Intravenous Route (Slight Modication of Bier's Method) Anesthesiology 7:558-560. (67) Hoyle JR. 1964. "Tourniquet for Intravenous Regional Anlalgesia. Anaestesia 19:294-295. (68) Bruner JM. 1951. Safety Factors in the use of the pneurmatic tourniquet for hemostasis in sur~ery of the hand, Jourrnal of Bone and Joit Srry 33A221-224. (69) Wilis EFS. 1971. Ob~servations on the effects of tourniquect ischenia, Joutrnal of Bone ndr Joint SurRPY 53A: 1343-1346. (70) Miller SH. I~ung RJ, et al. 1978. The Acute Effects of Tourniquet Ischeia on Tissue and Blood Gas Tensions in the Primate I.imnb, I. Hnd SJrery 3(1) :11-20. (71) Aams JP. Wilia EFS. 1971. Observation of the effects of tourniqut ischemia, Joucrnl of Bone and Joint Srgery 5,3A: 1346. (72) Web~b WR. 19)6. ioloic Foundations of Srery, Surery Cliics of Northi Aerca 45:267-287. (73) Fine J, Frank HA, Seliman AM. 1944. Tramatic Shock Journal of the American Association of Nurse Anesthetists VIII. Studies in the Therapy and Hemodynamics of Tourniquet Shock. Journal of Clinical Investigation, 23:731. (74) Fowler TJ, Danta G, Gilliatt RW. 1972. Recovery of Nerve Conduction After a Pneumatic Tourniquet: Observations on the Hind-limb of the Baboon, J. Neurol. Neurosurg. Psychiat. 35:638. (75) Bruner JM. 1973. Time, Pressure, and Temperature Factors in the Safe Use of the Tourniquet, Hand 5:39-42. (76) Moldaver J. 1954. Tourniquet Paralysis Syndrome, Arch. Surg., 68:136-144. (77) Ochoa J, Fowler TJ, Gilliat RW. 1972. Anatomical Changes in Peripheral Nerves Compressed by a Pneumatic Tourniquet, J. Anatomy 113:433. (78) Lundborg G. 1970. Ischemic Nerve Injury: Experimental Studies on Intraneuronal Microvascular Pathophysiology and Nerve Function in a Limb Subjected to Temporary Circulatory Arrest: Scand. J. Plastic Reconstr. Surg. 4 (Supp 6):91-106. Thomassen EH. 1978. An Improved Method of Applica(79) tion of the Pneumatic Tourniquet on Extremities, Clinical Orthopaedics and Related Research 103:99-100. (80) Stewart JDM. 1975. Tourniquets, In: Traction and Orthopaedic Appliances, Churchill Livingstone, New York, p. 181. (81) Mullick S. 1977. Low leg Tourniquet, West Ind. Med. J., 26:182. (82) Flatt AE. 172. Tourniquet Time in Hand Surgery, Arch Surg. 104:190-192. (83) Flewellen EH, Jarem B. 1978. Pneumatic Tourniquets, Anesthesiology Review 5:31-34. (84) Smith H. 1971. Surgical Technique, In: Campbell's Operative Orthopaedics.5th ed. Vol. 1, C.V. Mosby Co., St. Louis p. 19. (85) Nobel W, Black D, Johnson P, Kase C. 1974. Effect of Chronic Compression on the Microcirculation and Function of Peripheral Nerves. Proceedings of the International Symposium, Berlin, Sept. 1973, ed. J. Cervos-Navarra. Walter de Gruyter, New York, p. 483. (86) Sanders R. 1973. The Tourniquet. Instrument or Weapon? Hand 5(2) :119-123. (87) Thorn-Alquist AM. 1971. Intravenous Regional Anaesthesia: A Seven-Year Survey. Acta. Anaesth. Scandinav. 15:23-32. (88) Mullick S. 1978. The Tourniquet in Operations upon the Extremities. Surg. Gynecol. Obstet. 146:823-826. (89) Giesecke H. 1976. Anesthesia for the Surgery of Trauma, F.A. Davis Co., Philadelphia, p. 52-53. (90) Cole F. 1952. Tourniquet Pain, Anesthesia and Analgesia 31:63-64. (91) Haas LM, Lnadeen FH. 1979. Improved Intravenous Regional Anesthesia for Surgery of the Hand, Wrist, and Forearm: The Second Wrap Technique, J. Hand Surgery 3 (2) :194-195. (92) Rousso M. Wexler MR, Weinberg H, et al. 1978. Subcutaneous Ring Anaesthesia in the Prevention of Tourniquet Pain in Hand Surgery, J. Hand Surgery 10(3) :317-320. (93) Kuntz A. 1951. Afferent Innervation of Peripheral Blood Vessels Through Sympathetic Trunks, Southern Medical Journal 44 (8) :673-678. (94) Threadgill FD, Solnitzky O. 1949. Anatomical Studies of Afferency Within the Lumbosacral Sympathetic Ganglia. Anat. Rec. 103:96. (95) Bier A. 1901. Ueber Venenanaesthesie Berlinger klin Wochenschr. 46:477. (96) Knapp RB, Weinberg M. 1969. Distribution of Radioactive Local Anesthetics Following Intravenous Regional Anesthesia, Acta. Anaes. Scandinav. Supplementum XXXVI pg. 121-126. (97) Atkinson DL. 1969. The Mode of Action of Intravenous Regional Anesthetics. Acta. Anaes. Scandinav. Supplementum XXXVI p. 131-134. August/1981 (98) Miles DW, James JL, Clark DE. et al. 1964. Site of action of Intravenous Regional Anesthesia. J. Neurol. Neurosurg. Psychiatry 27:574-576. (99) Allen FM, Crossman LW, Lyons LV. 1946. Intravenous Procaine Analgesia, Anesthesia and Analgesia 25:1-9. (100) Harvey A. 1939. The Actions of Procaine on Neuromuscular Transmission, Bull. Johns Hopkins Hospital 65:223-238. (101) Jaco NT, Wood DR. 1944. The Interaction between Procaine, Cocaine, Adrenaline and Prostigmine on Skeletal Muscle, J. Pharmacol.Exp. Ther, 82:63-73. (102) Fujita T, Miyazaki M. 1968. A Comparative Study of Various Local Anesthetic Agents in Intravenous Regional Anesthesia, Anesthesia and Analgesia 47(5): 575-586. (103) Cotev S. 1966. Experimental Studies On Intravenous Regional Anaesthesia Using Radioactive Lignocaine. Br. J. Anaesthesia 38:936-939. (104) Cotev S, Robin GC. 1969. Experimental Studies on Intravenous Regional Using Radioactive Lidocaine. Acta. Anaes. Scandinav.-Supplementum XXXVI p. 127-130. (105) Shanks CA. 1970. Nerve Conduction Studies in Regional Intravenous Analgesia Using 1 Per Cent Lignocaine, Br. J. Anaesthesia 42:1060-1065. (106) DeJong R. 1970. Physiology and Pharmacology of Local Anesthesia, Charles C Thomas Co., Springfield, Ill. (107) Collins VJ. 1979. Principles of Anesthesiology, 2nd Ed. Lea and Febiger, Philadelphia, p. 877, 873. AUTHOR Commander Charles A. Reese, CRNA, PhD, USN, received his BSN from the University of Oklahoma and his BS in Nurse Anesthesia from George Washington University in Washington, DC. He received his MBA in Health Services Management from the National University in San Diego, California, and his PhD in Hospital/Health Services Administration from California Pacific University in San Diego. Dr. Reese has published extensively on the subject of regional anesthesia, and he has made numerous presentations on clinical anesthesia care. At the present time, he serves as the sole anesthetist aboard the nuclear aircraft carrier USS Nimitz, which is currently deployed in the Mediterranean Sea. Prior to his present assignment, Dr. Reese served on the AANA Continuing Education and Education Committees. He is currently a member of the AANA Journal's Editorial Advisory Board. This article was written while Dr. Reese was the Clinical Coordinator of the U.S. Navy Nurse Corps Anesthesia School at the Naval Regional Medical Center in Portsmouth, Virginia. The author wishes to state that the opinions or assertions contained in his article are his private views and are not to be construed as official and/or reflecting the views of the Department of Anesthesia, USS Nimitz, the Navy Nurse Corps, the Department of the Navy, or the Department of Defense.